The VALIDATE-D Study (VALIDATE-D)

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A total of 41 participants were consented to participate. Subsequently, 13 were found ineligible, 5 withdrew participation, 3 were lost-to follow-up, and 2 were withdrawn for non-compliance with the washout. Therefore, 18 were randomized.

Pre-assignment Details

An anti-hypertensive medication washout was conducted to minimize confounding of the renin-angiotensin system.

Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Subjects will receive placebo for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Period Title: Overall Study

Started

9

9

Sodium Restriction Baseline Visit [1]

9

9

Sodium Loading Baseline Visit [2]

9

9

Post-randomization Sodium Restriction [3]

9

9

Post-Randomization Sodium Loaded [4]

9

9

Completed

9

9

Not Completed

0

0

[1]

The first study visit was a pre-randomization assessment while sodium restricted (Baseline)

[2]

The second study visit was a pre-randomization assessment while sodium loaded (Baseline)

[3]

This visit was an assessment while sodium restricted and following 3 weeks of study medication

[4]

This visit was an assessment while sodium loaded and following 3 weeks of study medication

Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Subjects will receive placebo for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy

Description

The below results represent the change in Plasma Renin Activity.

Description

The below results represent the change in Plasma Renin Activity.

Time Frame

baseline and 2 weeks following calcitriol/placebo therapy

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

[Not Specified]

Arm/Group Title

Calcitriol

Placebo

Arm/Group Description:

Subjects have their plasma renin ac...

Subjects have their plasma renin ac...

Arm/Group Description:

Subjects have their plasma renin activity assessed at baseline while sodium restricted, and again after 2 weeks of randomized therapy with calcitriol (up to 0.75 mcg daily) or placebo.

Subjects have their plasma renin activity assessed at baseline while sodium restricted, and again after 2 weeks of randomized therapy with calcitriol (up to 0.75 mcg daily) or placebo.

Overall Number of Participants Analyzed

9

9

Median (Inter-Quartile Range)

Unit of Measure: ng/mL/h

0

(-1.3 to 0.3)

-1.3

(-3.6 to -0.3)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Calcitriol, Placebo

Comments

The hypothesis was that calcitriol therapy would lower plasma renin activity (PRA), when sodium restricted, when compared to placebo.

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.69

Comments

[Not Specified]

Method

ANOVA

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Median Difference (Final Values)

Estimated Value

1.3

Estimation Comments

[Not Specified]

2.Secondary Outcome

Title

Change in Renal Plasma Flow After Calcitriol/Placebo Therapy

Description

Subjects had their renal plasma flow assessed at baseline while sodium...

Description

Subjects had their renal plasma flow assessed at baseline while sodium loaded, and again after 3 weeks of randomized therapy with either calcitriol (up to 0.75 mcg daily) or placebo.

Time Frame

baseline and 3 weeks following calcitriol/placebo therapy

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

[Not Specified]

Arm/Group Title

Calcitriol

Placebo

Arm/Group Description:

Subjects have their renal plasma fl...

Subjects have their renal plasma fl...

Arm/Group Description:

Subjects have their renal plasma flow assessed at baseline while sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat renal plasma flow assessments again while sodium loaded.

Subjects have their renal plasma flow assessed at baseline while sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat renal plasma flow assessments again while sodium loaded.

Overall Number of Participants Analyzed

9

9

Mean (Standard Deviation)

Unit of Measure: mL/min/1.73m2

-16.4
(180.5)

-0.6
(142.2)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Calcitriol, Placebo

Comments

The hypothesis was that calcitriol therapy would raise renal plasma flow, when sodium loaded, when compared to placebo.

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.89

Comments

[Not Specified]

Method

ANOVA

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Mean Difference (Final Values)

Estimated Value

15.8

Estimation Comments

[Not Specified]

3.Secondary Outcome

Title

Change in Urine Protein After Calcitriol/Placebo Therapy

Description

Subjects have their urine protein assessed at baseline while sodium lo...

Description

Subjects have their urine protein assessed at baseline while sodium loaded and again 3 weeks after randomized therapy with calcitriol or placebo.

Time Frame

baseline and 3 weeks following calcitriol/placebo therapy

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

[Not Specified]

Arm/Group Title

Calcitriol

Placebo

Arm/Group Description:

Subjects have their urine protein a...

Subjects have their urine protein a...

Arm/Group Description:

Subjects have their urine protein assessed at baseline while sodium sodium loaded and again following 3 weeks of randomization to calcitriol (up to 0.75 mcg daily) or placebo.

Subjects have their urine protein assessed at baseline while sodium sodium loaded and again following 3 weeks of randomization to calcitriol (up to 0.75 mcg daily) or placebo.

Overall Number of Participants Analyzed

9

9

Mean (Standard Deviation)

Unit of Measure: mg/24h

21.1
(95.7)

8.1
(51.0)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Calcitriol, Placebo

Comments

The hypothesis was that calcitriol therapy would lower urine protein, when sodium loaded, when compared to placebo.

This was a small physiological study, not a treatment study or a typical Phase 1-4 study. The objective was to investigate the mechanistic link between vitamin D receptor agonist therapy and the renin-angiotensin system.